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Tissue transglutaminase and apoptosis: sense and antisense transfection studies with human neuroblastoma cells.

Department of Experimental Medicine, University of Rome Tor Vergata, Italy.

ABSTRACT

In this report, we show that the overexpression of tissue transglutaminase (tTG) in the human neuroblastoma cell line SK-N-BE(2) renders these neural crest-derived cells highly susceptible to death by apoptosis. Cells transfected with a full-length tTG cDNA, under the control of a constitutive promoter, show a drastic reduction in proliferative capacity paralleled by a large increase in cell death rate. The dying tTG-transfected cells exhibit both cytoplasmic and nuclear changes characteristic of cells undergoing apoptosis. The tTG-transfected cells express high Bcl-2 protein levels as well as phenotypic neural cell adhesion molecule markers (NCAM and neurofilaments) of cells differentiating along the neuronal pathway. In keeping with these findings, transfection of neuroblastoma cells with an expression vector containing segments of the human tTG cDNA in antisense orientation resulted in a pronounced decrease of both spontaneous and retinoic acid (RA)-induced apoptosis. We also present evidence that (i) the apoptotic program of these neuroectodermal cells is strictly regulated by RA and (ii) cell death by apoptosis in the human neuroblastoma SK-N-BE(2) cells preferentially occurs in the substrate-adherent phenotype. For the first time, we report here a direct effect of tTG in the phenotypic maturation toward apoptosis. These results indicate that the tTG-dependent irreversible cross-linking of intracellular protein represents an important biochemical event in the induction of the structural changes featuring cells dying by apoptosis.

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• Joseph, B., Lefebvre, O., Mereau-Richard, C., Danze, P.-M., Belin-Plancot, M.-T., Formstecher, P. (1998). Evidence for the Involvement of Both Retinoic Acid Receptor- and Retinoic X Receptor-Dependent Signaling Pathways in the Induction of Tissue Transglutaminase and Apoptosis in the Human Myeloma Cell Line RPMI 8226 . Blood 91: 2423-2432 [Abstract] [Full Text]  
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• Zhang, J., Lesort, M., Guttmann, R. P., Johnson, G. V. W. (1998). Modulation of the in Situ Activity of Tissue Transglutaminase by Calcium and GTP. J. Biol. Chem. 273: 2288-2295 [Abstract] [Full Text]  
• Lai, T.-S., Slaughter, T. F., Peoples, K. A., Hettasch, J. M., Greenberg, C. S. (1998). Regulation of Human Tissue Transglutaminase Function by Magnesium-Nucleotide Complexes. IDENTIFICATION OF DISTINCT BINDING SITES FOR Mg-GTP AND Mg-ATP. J. Biol. Chem. 273: 1776-1781 [Abstract] [Full Text]  
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